The well known complications of blood transfusion, namely incompatibility reactions, disease transmission, immunosuppression and the storage limitations of erythrocytes points to the need for the development of blood substitutes devoid of these shortcomings. The limited availability of certain antigenic blood types and the scarcity of blood products in certain facilities, such as field hospitals also indicate a need for a blood substitute with a more dependable supply chain. Blood substitutes will have numerous applications provided they are safe, meet the viscosity and flow requirements, have the necessary in vivo and shelf life and are cost effective.
It is well known that the hemoglobin molecule is present in erythrocytes and acts as the agent for the transport of oxygen in mammalian circulatory systems by binding and releasing oxygen. Hemoglobin is a conjugated protein with an approximate molecular weight of 64,000. It contains basic proteins, the globins and ferroprotoporphyrin or heme. It is essentially a tetramer consisting of two alpha chains, each containing 141 amino acids, and two beta chains, each containing 146 amino acids. The binding site for oxygen in each of the monomers which make up the tetramer is the Fe(II) molecule in the heme molecule.
Various properties of hemoglobin have been investigated for use in blood substitute products. The four primary issues with Hemoglobin-Based Oxygen Carriers (HBOCs) are the disassociation of the hemoglobin tetramer, the production of free oxygen radicals, the scavenging of nitric oxide, and finally the inactivation of hemoglobin into methemoglobin. While solutions to the first three problems have been proposed, the last problem has not been adequately addressed to permit the use of HBOCs as a viable tool in blood substitution.